Cargando…

Overexpression of Fkbp11, a feature of lupus B cells, leads to B cell tolerance breakdown and initiates plasma cell differentiation

Systemic Lupus Erythematosus (SLE) is a severe systemic autoimmune disease, characterized by multi-organ damages, triggered by an autoantibody-mediated inflammation, and with a complex genetic influence. It is today accepted that adult SLE arises from the building up of many subtle gene variations,...

Descripción completa

Detalles Bibliográficos
Autores principales: Ruer-Laventie, Julie, Simoni, Léa, Schickel, Jean-Nicolas, Soley, Anne, Duval, Monique, Knapp, Anne-Marie, Marcellin, Luc, Lamon, Delphine, Korganow, Anne-Sophie, Martin, Thierry, Pasquali, Jean-Louis, Soulas-Sprauel, Pauline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578525/
https://www.ncbi.nlm.nih.gov/pubmed/26417441
http://dx.doi.org/10.1002/iid3.65
_version_ 1782391130282786816
author Ruer-Laventie, Julie
Simoni, Léa
Schickel, Jean-Nicolas
Soley, Anne
Duval, Monique
Knapp, Anne-Marie
Marcellin, Luc
Lamon, Delphine
Korganow, Anne-Sophie
Martin, Thierry
Pasquali, Jean-Louis
Soulas-Sprauel, Pauline
author_facet Ruer-Laventie, Julie
Simoni, Léa
Schickel, Jean-Nicolas
Soley, Anne
Duval, Monique
Knapp, Anne-Marie
Marcellin, Luc
Lamon, Delphine
Korganow, Anne-Sophie
Martin, Thierry
Pasquali, Jean-Louis
Soulas-Sprauel, Pauline
author_sort Ruer-Laventie, Julie
collection PubMed
description Systemic Lupus Erythematosus (SLE) is a severe systemic autoimmune disease, characterized by multi-organ damages, triggered by an autoantibody-mediated inflammation, and with a complex genetic influence. It is today accepted that adult SLE arises from the building up of many subtle gene variations, each one adding a new brick on the SLE susceptibility and contributing to a phenotypic trait to the disease. One of the ways to find these gene variations consists in comprehensive analysis of gene expression variation in a precise cell type, which can constitute a good complementary strategy to genome wide association studies. Using this strategy, and considering the central role of B cells in SLE, we analyzed the B cell transcriptome of quiescent SLE patients, and identified an overexpression of FKBP11, coding for a cytoplasmic putative peptidyl-prolyl cis/trans isomerase and chaperone enzyme. To understand the consequences of FKBP11 overexpression on B cell function and on autoimmunity's development, we created lentiviral transgenic mice reproducing this gene expression variation. We showed that high expression of Fkbp11 reproduces by itself two phenotypic traits of SLE in mice: breakdown of B cell tolerance against DNA and initiation of plasma cell differentiation by acting upstream of Pax5 master regulator gene.
format Online
Article
Text
id pubmed-4578525
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher John Wiley & Sons, Ltd
record_format MEDLINE/PubMed
spelling pubmed-45785252015-09-28 Overexpression of Fkbp11, a feature of lupus B cells, leads to B cell tolerance breakdown and initiates plasma cell differentiation Ruer-Laventie, Julie Simoni, Léa Schickel, Jean-Nicolas Soley, Anne Duval, Monique Knapp, Anne-Marie Marcellin, Luc Lamon, Delphine Korganow, Anne-Sophie Martin, Thierry Pasquali, Jean-Louis Soulas-Sprauel, Pauline Immun Inflamm Dis Original Research Systemic Lupus Erythematosus (SLE) is a severe systemic autoimmune disease, characterized by multi-organ damages, triggered by an autoantibody-mediated inflammation, and with a complex genetic influence. It is today accepted that adult SLE arises from the building up of many subtle gene variations, each one adding a new brick on the SLE susceptibility and contributing to a phenotypic trait to the disease. One of the ways to find these gene variations consists in comprehensive analysis of gene expression variation in a precise cell type, which can constitute a good complementary strategy to genome wide association studies. Using this strategy, and considering the central role of B cells in SLE, we analyzed the B cell transcriptome of quiescent SLE patients, and identified an overexpression of FKBP11, coding for a cytoplasmic putative peptidyl-prolyl cis/trans isomerase and chaperone enzyme. To understand the consequences of FKBP11 overexpression on B cell function and on autoimmunity's development, we created lentiviral transgenic mice reproducing this gene expression variation. We showed that high expression of Fkbp11 reproduces by itself two phenotypic traits of SLE in mice: breakdown of B cell tolerance against DNA and initiation of plasma cell differentiation by acting upstream of Pax5 master regulator gene. John Wiley & Sons, Ltd 2015-09 2015-06-18 /pmc/articles/PMC4578525/ /pubmed/26417441 http://dx.doi.org/10.1002/iid3.65 Text en © 2015 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd. Published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Ruer-Laventie, Julie
Simoni, Léa
Schickel, Jean-Nicolas
Soley, Anne
Duval, Monique
Knapp, Anne-Marie
Marcellin, Luc
Lamon, Delphine
Korganow, Anne-Sophie
Martin, Thierry
Pasquali, Jean-Louis
Soulas-Sprauel, Pauline
Overexpression of Fkbp11, a feature of lupus B cells, leads to B cell tolerance breakdown and initiates plasma cell differentiation
title Overexpression of Fkbp11, a feature of lupus B cells, leads to B cell tolerance breakdown and initiates plasma cell differentiation
title_full Overexpression of Fkbp11, a feature of lupus B cells, leads to B cell tolerance breakdown and initiates plasma cell differentiation
title_fullStr Overexpression of Fkbp11, a feature of lupus B cells, leads to B cell tolerance breakdown and initiates plasma cell differentiation
title_full_unstemmed Overexpression of Fkbp11, a feature of lupus B cells, leads to B cell tolerance breakdown and initiates plasma cell differentiation
title_short Overexpression of Fkbp11, a feature of lupus B cells, leads to B cell tolerance breakdown and initiates plasma cell differentiation
title_sort overexpression of fkbp11, a feature of lupus b cells, leads to b cell tolerance breakdown and initiates plasma cell differentiation
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578525/
https://www.ncbi.nlm.nih.gov/pubmed/26417441
http://dx.doi.org/10.1002/iid3.65
work_keys_str_mv AT ruerlaventiejulie overexpressionoffkbp11afeatureoflupusbcellsleadstobcelltolerancebreakdownandinitiatesplasmacelldifferentiation
AT simonilea overexpressionoffkbp11afeatureoflupusbcellsleadstobcelltolerancebreakdownandinitiatesplasmacelldifferentiation
AT schickeljeannicolas overexpressionoffkbp11afeatureoflupusbcellsleadstobcelltolerancebreakdownandinitiatesplasmacelldifferentiation
AT soleyanne overexpressionoffkbp11afeatureoflupusbcellsleadstobcelltolerancebreakdownandinitiatesplasmacelldifferentiation
AT duvalmonique overexpressionoffkbp11afeatureoflupusbcellsleadstobcelltolerancebreakdownandinitiatesplasmacelldifferentiation
AT knappannemarie overexpressionoffkbp11afeatureoflupusbcellsleadstobcelltolerancebreakdownandinitiatesplasmacelldifferentiation
AT marcellinluc overexpressionoffkbp11afeatureoflupusbcellsleadstobcelltolerancebreakdownandinitiatesplasmacelldifferentiation
AT lamondelphine overexpressionoffkbp11afeatureoflupusbcellsleadstobcelltolerancebreakdownandinitiatesplasmacelldifferentiation
AT korganowannesophie overexpressionoffkbp11afeatureoflupusbcellsleadstobcelltolerancebreakdownandinitiatesplasmacelldifferentiation
AT martinthierry overexpressionoffkbp11afeatureoflupusbcellsleadstobcelltolerancebreakdownandinitiatesplasmacelldifferentiation
AT pasqualijeanlouis overexpressionoffkbp11afeatureoflupusbcellsleadstobcelltolerancebreakdownandinitiatesplasmacelldifferentiation
AT soulassprauelpauline overexpressionoffkbp11afeatureoflupusbcellsleadstobcelltolerancebreakdownandinitiatesplasmacelldifferentiation